[Multiple-dose pharmacokinetics of paracetamol and salicylamide in man after combined rectal application (author's...

The pharmacokinetic behaviour of paracetamol (300 mg) and salicylamide (200 mg) in the course of combined repetitive (three times tau = 4 h) administration of suppositories was investigated in 10 healthy, male volunteers. The estimation of the pharmacokinetic constants was performed by a simultaneous curve fitting from all single values with a direct search procedure, based on an open two-compartment model and the multiple-dose equation. Both drugs showed a pharmacokinetic behaviour which was conformable to the literature data for single dose and mono substance applications. The dynamics of the absorption kinetics was decreased, as is generally seen after the application of suppositories. In spite of this both substances reached a steady state after the 3rd application. A calculation of collapse coefficients showed for paracetamol as well as for salicylamide a pharmacokinetic distribution behaviour deviating from an open one-compartment model. Due to the good conformity of the parameters, which causes the synchronism of the time-concentration curves after multiple dose application, paracetamol and salicylamide are suited combination partners as seen from a pharmacokinetic point of view.